rs863223321

chr16-89280587-CTG-C

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_013275.6(ANKRD11):c.5953_5954del(p.Gln1985GlufsTer46) variant causes a frameshift change. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD11 NM_013275.6 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.53

Genes affected

ANKRD11 (HGNC:21316): (ankyrin repeat domain containing 11) This locus encodes an ankryin repeat domain-containing protein. The encoded protein inhibits ligand-dependent activation of transcription. Mutations in this gene have been associated with KBG syndrome, which is characterized by macrodontia, distinctive craniofacial features, short stature, skeletal anomalies, global developmental delay, seizures and intellectual disability. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 2 and X. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 16-89280587-CTG-C is Pathogenic according to our data. Variant chr16-89280587-CTG-C is described in ClinVar as [Pathogenic]. Clinvar id is 30892.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-89280587-CTG-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD11	NM_013275.6	c.5953_5954del	p.Gln1985GlufsTer46	frameshift_variant	9/13	ENST00000301030.10
ANKRD11	NM_001256182.2	c.5953_5954del	p.Gln1985GlufsTer46	frameshift_variant	10/14
ANKRD11	NM_001256183.2	c.5953_5954del	p.Gln1985GlufsTer46	frameshift_variant	9/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD11	ENST00000301030.10	c.5953_5954del	p.Gln1985GlufsTer46	frameshift_variant	9/13	5	NM_013275.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

KBG syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 12, 2011

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs863223321; hg19: chr16-89346995;